A5045091140- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Kruppel-like factors research
- Chronic Myeloid Leukemia Treatments
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Cell death mechanisms and regulation
- Platelet Disorders and Treatments
- Cancer Genomics and Diagnostics
- Sarcoma Diagnosis and Treatment
- Testicular diseases and treatments
- CRISPR and Genetic Engineering
- Blood groups and transfusion
- RNA regulation and disease
- Eosinophilic Disorders and Syndromes
- Endoplasmic Reticulum Stress and Disease
- Viral Infections and Immunology Research
- Epigenetics and DNA Methylation
- Medicinal Plant Pharmacodynamics Research
- interferon and immune responses
- Cell Adhesion Molecules Research
- Lymphoma Diagnosis and Treatment
- Cardiomyopathy and Myosin Studies
- PI3K/AKT/mTOR signaling in cancer
- RNA modifications and cancer
The University of Melbourne
2012-2025
de Duve Institute
2017-2023
Walloon Excellence in Lifesciences and Biotechnology
2020-2023
Ludwig Cancer Research
2016-2021
UCLouvain
2020-2021
Walter and Eliza Hall Institute of Medical Research
2012-2020
Protein kinase-like domains that lack conserved residues known to catalyse phosphoryl transfer, termed pseudokinases, have emerged as important signalling across all kingdoms of life. Although predicted function principally catalysis-independent protein-interaction modules, several pseudokinase been attributed unexpected catalytic functions, often amid controversy. We established a thermal-shift assay benchmark technique define the nucleotide-binding properties domains. Unlike in vitro...
The pseudokinase MLKL (mixed lineage kinase domain-like), has recently emerged as a critical component of the necroptosis cell death pathway. Although it is clear that phosphorylation activation loop in domain by upstream protein RIPK3 (receptor-interacting kinase-3), crucial to trigger activation, remained unclear whether other events modulate function. By reconstituting Mlkl−/−, Ripk3−/− and Mlkl−/−Ripk3−/− cells with phospho-site mutants, we compared function known sites regulating three...
Abstract MLKL is the essential effector of necroptosis, a form programmed lytic cell death. We have isolated mouse strain with single missense mutation, Mlkl D139V , that alters two-helix ‘brace’ connects killer four-helix bundle and regulatory pseudokinase domains. This confers constitutive, RIPK3 independent killing activity to MLKL. Homozygous mutant mice develop lethal postnatal inflammation salivary glands mediastinum. The normal embryonic development homozygotes until birth, absence...
The integration of whole-genome sequencing (WGS) and whole-transcriptome (WTS) has revolutionized cancer diagnostics, enabling comprehensive molecular profiling tumours. While WGS uncovers genomic alterations such as single nucleotide variants (SNVs), structural (SVs), copy number changes, WTS provides complementary insights into transcriptomic including gene expression levels, alternative splicing, fusion events. Together, these technologies offer unparalleled potential to guide precision...
JAK2 (Janus kinase 2) initiates the intracellular signalling cascade downstream of cell surface receptor activation by cognate haemopoietic cytokines, including erythropoietin and thrombopoietin. The pseudokinase domain (JH2) negatively regulates catalytic activity adjacent tyrosine (JH1) mutations within underlie human myeloproliferative neoplasms, polycythaemia vera essential thrombocytosis. To date, mechanism JH2-mediated inhibition JH1 as well susceptibility pathological mutant to...
Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYAs) sarcoma unique understudied patient population have only achieved modest survival gains compared to other groups. We present our institutional experience AYAs who underwent comprehensive molecular profiling (CMP) via either large-panel targeted DNA sequencing or whole genome transcriptome evaluated the feasibility clinical impact this approach....
Activation of the cell surface receptor, c-Mpl, by cytokine, thrombopoietin (TPO), underpins megakaryocyte and platelet production in mammals. In humans, mutations c-Mpl have been identified as molecular basis Congenital Amegakaryocytic Thrombocytopenia (CAMT). Here, we show that CAMT-associated principally lead to defective receptor presentation on surface. contrast, one CAMT mutant F104S, was expressed surface, but showed TPO binding activation. Using mutational analyses, examined which...
Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYA) sarcoma unique under-studied patient population have only achieved modest survival gains compared to other groups. We present our institutional experience AYA who underwent comprehensive molecular profiling (CMP) using either large-panel targeted DNA sequencing or whole genome transcriptome evaluated the feasibility clinical impact this...